This research proposal will focus on a systematic study of the physiological relationships between two major endocrine systems, the adrenal and the gonadal systems. The studies will attempt to understand the role of the hypothalamo-pituitary-adrenal axis in the physiology of the menstrual cycle, and in the etiology of the hypothalamic amenorrhea syndrome. The animal model used will be the female rhesus monkey, a species which has menstrual cycles similar to the human. There are 4 specific aims. Aim 1 is to demonstrate an inhibitory control by CRF of the reproductive axis. The objectives here will be to demonstrate that CRF inhibits LH and/or FSH secretion in the ovariectomized monkey, to investigate whether this effect requires an adrenal component, such as an increase in cortisol secretion, and to find out whether there is a relationship between endogenous CRF release and LH/FSH secretion. Aim 2 is to demonstrate a permissive role of the adrenal axis on reproductive function. This will be done by investigating whether CRF or adrenal secretion may, under normal physiological circumstances, influence gonadotropin secretion in such a way as to facilitate normal reproductive function. The specific objectives will be to demonstrate whether CRF release from the hypothalamus varies with the ovarian endocrine milieu and whether antagonism of endogenous CRF activity interferes with the normal physiology of the menstrual cycle. Aim 3 is to study the site and mechanism of action of CRF and cortisol in their effects on gonadotropin secretion. The objectives will be to investigate whether these compounds affect LH by acting at a central site, or at a pituitary site. If a central site of action is demonstrated, a role of the endogenous opiates in this process will be investigated. Studies on a pituitary site of action will involve pituitary stalk sectioned monkeys under controlled GnRH replacement therapy. Aim 4 will examine the role of CRF and glucocorticoids it the pathology of the menstrual cycle, and more specifically, whether they participate in the etiology of the hypothalamic amenorrhea syndrome.